The two known forms of cellular death are necrosis and apoptosis. Apoptosis is the biological process of controlled, programmed cell death, by means of which cells die by a process of condensation without the release of cell contents into the surrounding milieu. Cells of most organs and tissues divide and multiply over time, a process that is normally in equilibrium with cell death by apoptosis, resulting in optimal cell numbers in the healthy body, Apoptosis, therefore, can be considered to act as a control on the total number of cells in organs and tissues. Residues of apoptosed cells are largely consumed by other cells, by a process of phagocytosis. The process of apoptosis, the natural, well-regulated process by which the body undertakes removal of unwanted cells is to be contrasted with the process of necrosis by which the cells die largely in an uncontrolled manner, as a result of membrane rupture. Importantly, however, in many instances apoptosis and necrosis behave as a continuum. The intracellular components of necrosed cells are released into the organism in an uncontrolled manner, commonly resulting in inflammatory reactions as the body attempts to deal with these suddenly encountered components. Apoptosed cells cause virtually no harmful inflammatory reactions.
Some medical disorders in a living body, or an individual organ of a living body, can be attributed at least in part to an undue acceleration in the rate of apoptosis. This can occur, for example, when a body ingests chemical poisons or encounters excessive amounts of harmful radiation (radioactivity, UV exposure, etc.). Other disorders involve both apoptosis and necrosis. Still other disorders involve an accelerated rate of cell death due primarily to necrosis.
Apoptosis of the cell is understood to be initiated by an alteration in the functioning of the mitochondria of the cell. Mitochondria, as is well known, are membrane-bounded organelles, located within the cell, and occupying a major fraction of the total cell volume. They contain large amounts of internal membrane. The main function of mitochondria is to convert energy from foodstuffs to forms that can be used to drive cellular reactions. This is accomplished by a process of chemiosmotic coupling, by which membrane-bound ion pumps transfer ions from one side of the mitochondrial membrane to the other. The proton pumps generate an electrochemical proton gradient across the membrane, which is used to drive various energy-requiring reactions when the protons flow through membrane embedded proteins such as the enzyme ATP synthase. As an ionic process, the potential across the mitochondrial membrane is important in the efficient operation of this energy-providing mechanism. Mitochondria participate directly in the induction of apoptosis by releasing pro-apoptotic proteins. Decreases in mitochondrial membrane potential are known to be indicative of the commencement of apoptosis.
Organs undergoing apoptosis exhibit oligonucleosomal DNA fragmentation into 180–200 base pairs, in a specific pattern which appears as a ladder after gel electrophoresis. The degree of DNA fragmentation correlates with the progression of apoptosis in the organ, and can be measured by extracting the DNA, radiolabelling it, subjecting it to electrophoresis and quantifying the radioactivity associated with various DNA fragments. Such techniques can be used to determine the numbers of cells undergoing apoptosis or exhibiting an apoptotic condition or predisposition, so as to determine an extent or degree of apoptosis in a body organ or tissue.
In the course of necrosis, enzymes and other cell contents normally contained in the cytoplasm are released, as a result of disintegration of cell membranes, a hallmark of necrosis. One of these is the enzyme lactate dehydrogenase (LDH), the levels of which are commonly used to determine the degree of necrosis.